Our specific goals of this research are to understand the structural basis of function by designing and evaluating mutant forms of the G proteins and receptors. The CGL facilities are crucial for many steps of our research including viewing crystallographic or modelled structures to design mutants, rationalizing the properties of the mutants, and to develop hypotheses about protein-ligand and protein-protein interactions, and about conformational changes involved in activation and deactivation. We are studying the structure and function of signal transduction proteins, specifically heterotrimeric GTP-binding proteins (G proteins) and G protein-coupled receptors (GPCRs). When an agonist such as a hormone or neurotransmitter binds its receptor, exchange of GTP for GDP bound to the G protein is catalyzed. The GTP-bound alpha subunit of the G protein separates from the beta-gamma subunit complex, and each of these can go on to stimulate downstream effectors. The hydrolysis of GTP to GDP by the alpha subunit and subsequent heterotrimer reassembly turns off the signal. While the structures of some G protein subunits have been solved, atomic-level structures have not been determined for the receptors.